Radium-223 Calibration Sue Hooper Principal Physicist Nuclear Medicine Velindre NHS Trust
What is Ra-223? Ra-223 (Alpharadin) is an alpha emitting radionuclide -supplied by Algeta ASA in Norway 227 Ac 227 Th 223 Ra
Why use Ra-223? It is being used in a phase II, multicentre study for the palliation of painful bone metastases in hormone refractory prostate cancer patients cf Sr-89 (Metastron) and Sm-153 (Quadramet) - both β emitters
Range in tissue Tissue range for 223 Ra < 100 µm (α) Cf Tissue range for 89 Sr < 8mm (β) Quality F actor: α particles = 20 γ rays & β particles =1
Activities of Ra-223 involved Patients are entered into one of four randomisation arms: 5, 25, 50 or 100 kbq/kg
Physical Properties of T ½ = 11.43 days Ra-223 α energy (average) = 5.78 MeV (accounts for 93.5% of emitted energy); <4% as β particles; <2% as γ radiation β energy/decay: 1MeV (ave) γ energy/decay: 0.4 MeV γ energy: 269 kev (13.6%) 154 kev (6.04%) 324 kev (3.9%)
Decay Scheme of Ra-223 223 Ra 11.43 d 219 Rn 3.96 s 215 Po 1.78 ms α, 5.78 ΜeV α, 6.88 MeV Combined energy for the complete decay of Ra-223 & daughters = 28MeV 211 Pb 36.1 m α, 7.53 MeV β -, 0.45 MeV Some γ (0.9 MeV total) is also emitted 211 Bi 2.17 m α (99.727 %), 6.68 MeV β - (0.273 %), 0.01 MeV 207 Tl 4.77 m β -, 0.49 MeV 211 Po 516 ms α, 7.59 MeV Courtesy of Algeta 207 Pb stable
Container for Ra-223 20 ml glass vial Conc 500 or 1000 kbq/ml Maximum activity in vial =23 MBq Dose rate from unshielded vial outer wall: 100µSv/h/MBq 10cm from vial : 6µSv/h/MBq 100 cm from vial: 0.06 µsv/h/mbq
Calibration Procedure (SOP) The company send out a SOP Dial setting of Radioisotope Dose Calibrators for measurement of the radioisotope Radium-223 at clinical centres prior to clinical trials with Alpharadin.
Calibration Procedure (SOP) 1. Purpose - to find the dial setting for the Dose Calibrator! 2. Responsibility and Authority - tells you to follow SOP and return the results 3. Definitions None
Calibration Procedure (SOP) 4. Procedure : Scheme 1 is used to decay correct the activity in the Ra-223 solution Scheme 2 is used to document the affirmative measurements for the dial setting (more detail to follow)
Calibration Procedure (SOP) Perform standard QA & bkgd checks for calibrator Read stated activity of Ra-223 on label of vial. Use supplied Volume Correction chart to correct the stated activity for decay to the measuring time. Corr act = A c
Vol corr chart Days from ref date Vol. x factor (V mf ) -5 0.74-4 0.78-3 0.83-2 0.88-1 0.94 0 1 1 1.06 2 1.13 3 1.20 4 1.27
Calibration Procedure (SOP) Place the Ra-223 in the calibrator making sure it is centred in the measuring chamber Adjust the calibrator until it displays the decay corr activity A c Note the calibrator factor/setting for further measurements of unknown activity Perform 3 measurements with the Ra-223 standard source. Allow calibrator to return to bkgd between the measurements. All three measurements should be ± 5% of A c
Calibration Procedure (SOP) 5. References None 6. Revision First 7. Appendices Scheme 1 and Scheme 2
Calibrator at Velindre Capintec CRC15 Beta - consists of a chamber (for γ emitters) and a beta counter (for pure β emitters) - measurements of Ra-223 performed in the ionisation chamber
In practice! Receive vial of Ra-223 Activity (MBq) on date @ 1200 CET (no hours on decay chart so can only do approximate activity if measurements not made at this time) Our factor appeared to be between Cal #240 and Cal #250 (1 dec place)
In practice! Measurement repeated the following day at 12:00 (should have been 11:00!) Activity in vial calculated to 2 dec places using Vol Corr Chart. SPC button pressed to display 2 dec places on calibrator -factor then appeared to CAL #251 using the vial jig supplied with the calibrator.
Results Scheme 1-Decay correction of Ra-223 standard soln Stated Act (A) Calib date (std soln) Date of Calib of dose calib Decay corr act in std soln Ac= A x cf Ra-223 calib no/factor from vol corr table 6MBq 21.7.05 @12:00 13.7.05 @12:00 9.67MBq CAL #251
Results Scheme 2 Affirmative measurements Decay corrected Activity Activity Affirmative measurement 1 Activity Affirmative measurement 2 Activity Affirmative measurement 3 A c (MBq) (MBq) (MBq) (MBq) 9.67 9.62 9.60 9.76
In practice! Results faxed off to company no information ever received back if we were right or wrong despite me asking. As for syringe measurements. Every centre involved in the trial is using the same factor as derived for the vial. Our syringe jig drops activity down into calibrated part of the chamber. Purely go on volume dispensed. Vial activity means Ra- 223 solution in equilibrium, not necessarily the case for the syringe.
New Calibration SOP Purpose and Responsibility not changed much Definitions now defines a dose calibrator, sample calib date (prior to calib date the activity is higher than stated, after the activity is less), isotope calibration factor or number Procedure corr the std activity for decay according to the formula A c = A 0. e where ( - ln2 * d ) 11.43 A 0 is stated activity of the vial d = no of days (this number is below zero in the case where the dose calibrator dial setting is performed before the sample calibration date) Recording the measurements appears to be the same
New Calibration SOP References None Revision Second -changes from the first edition: The procedure for decay correction of the stated activity is converted from a correction based on a decay table to a direct decay correction by means of a standard decay formula for radioactive substance. Minor linguistic updates are performed. A user friendlier version of Scheme 1 and 2 is presented.